AIMS: The electrical properties of Na(+)-activated K(+) current (I(K(Na))) and its contribution to spike firing has not been characterized in motor neurons. METHODS: We evaluated how activation of voltage-gated K(+) current (I(K)) at the cellular level could be coupled to Na(+) influx through voltage-gated Na(+) current (I(N)(a)) in two motor neuron-like cells (NG108-15 and NSC-34 cells). RESULTS: Increasing stimulation frequency altered the amplitudes of both I(Na) and I(K) simultaneously. With changes in stimulation frequency, the kinetics of both I(Na) inactivation and I(K) activation were well correlated at the same cell. Addition of tetrodotoxin or ranolazine reduced the amplitudes of both I(Na) and I(K) simultaneously. Tefluthrin (Tef) increased the amplitudes of both I(Na) and I(K) throughout the voltages ranging from -30 to + 10 mV. In cell-attached recordings, single-channel conductance from a linear current-voltage relation was 94 ± 3 pS (n = 7). Tef (10 μm) enhanced channel activity with no change in single-channel conductance. Tef increased spike firing accompanied by enhanced facilitation of spike-frequency adaptation. Riluzole (10 μm) reversed Tef-stimulated activity of K(Na) channels. In motor neuron-like NSC-34 cells, increasing stimulation frequency altered the kinetics of both I(Na) and I(K). Modelling studies of motor neurons were simulated to demonstrate that the magnitude of I(K(Na)) modulates AP firing. CONCLUSIONS: There is a direct association of Na(+) and K(Na) channels which can provide the rapid activation of K(Na) channels required to regulate AP firing occurring in motor neurons.

To investigate the protective effects of curcumin against amyloid-β (Aβ)-induced neuronal damage. Primary rat cortical neurons were cultured with different treatments of Aβ and curcumin. Neuronal morphologies, viability and damage were assessed. Neuronal oxidative stress was assessed, including extracellular hydrogen peroxide and intracellular reactive oxygen species. The abilities of curcumin to scavenge free radicals and to inhibit Aβ aggregation and β-sheeted formation are further assessed and discussed. Curcumin preserves cell viability, which is decreased by Aβ. The results of changed morphology, released Lactate dehydrogenases and cell viability assays indicate that curcumin protects Aβ-induced neuronal damage. Curcumin depresses Aβ-induced up-regulation of neuronal oxidative stress. The treatment sequence impacts the protective effect of curcumin on Aβ-induced neuronal damage. Curcumin shows a more protective effect on neuronal oxidative damage when curcumin was added into cultured neurons not later than Aβ, especially prior to Aβ. The abilities of curcumin to scavenge free radicals and to inhibit the formation of β-sheeted aggregation are both beneficial to depress Aβ-induced oxidative damage. Curcumin prevents neurons from Aβ-induced oxidative damage, implying the therapeutic usage for the treatment of Alzheimer's disease patients.

BACKGROUND/PURPOSE Globus pharyngeus and dysphagia are common complaints of patients referred to ear, nose, and throat (ENT) clinics. We aimed to establish an efficient method to rule out the presence of malignancy in patients with globus pharyngeus and dysphagia. METHODS The use of flexible transnasal esophagoscopy (TNE) was evaluated in 30 patients with globus pharyngeus and 6 patients with dysphagia. The patients were immediately informed of the findings on TNE examination, and then treatments were planned. All patients were treated with lansoprazole for 2 weeks and provided education on lifestyle changes at the initial examination and at the 3-month follow-up. RESULTS The patients reported an improvement in symptoms of globus pharyngeus after treatment (p<0.001). Follow-up TNE confirmed improvement with less dysphagia, erythema, and vocal cord edema evident (all p<0.001). CONCLUSION The use of TNE and patient education are efficient management strategies for patients with symptoms of globus pharyngeus and dysphagia.

Development of SAR at the C2 position of indole lead 1, a palm site inhibitor of HCV NS5B polymerase (NS5B IC(50)=0.053μM, replicon EC(50)=4.8μM), is described. Initial screening identified an acyl sulfonamide moiety as an isostere for the C2 carboxylic acid group. Further SAR investigation resulted in identification of acyl sufonamide analog 7q (NS5B IC(50)=0.039μM, replicon EC(50)=0.011μM) with >100-fold improved replicon activity.

chang c.-w., huang h.-c., chiang c.-y., hsu c.-p.& chang c.-c.(2011) Social capital and knowledge sharing: effects on patient safety. Journal of Advanced Nursing00(0), 000-000. doi: 10.1111/j.1365-2648.2011.05871.x ABSTRACT: Aims.  This article is a report on a study that empirically examines the influence of social capital on knowledge sharing and the impact of knowledge sharing on patient safety. Background.  Knowledge sharing is linked to many desirable managerial outcomes, including learning and problem-solving, which are essential for patient safety. Rather than studying the tangible effects of rewards, this study examines whether social capital (including social interaction, trust and shared vision) directly supports individual knowledge sharing in an organization. Methods.  This cross-sectional study analysed data collected through a questionnaire survey of nurses from a major medical centre in northern Taiwan. The data were collected over a 9-month period from 2008 to 2009. The data analysis was conducted using the Partial Least Squares Graph v3.0 program to evaluate the measurement properties and the structural relationships specified in the research model. Findings.  Based on a large-scale survey, empirical results indicate that Registered Nurses' perceptions of trust and shared vision have statistically significant and direct effects on knowledge sharing. In addition, knowledge sharing is significantly and positively associated with patient safety. Conclusion.  The findings suggest that hospital administrators should foster group trust and initiate a common vision among Registered Nurses. In addition, administrators and chief knowledge officers of hospitals should encourage positive intentions towards knowledge sharing.

BACKGROUND Previous reports have indicated that insulin resistance (IR) is associated with chronic hepatits C virus (HCV) infection. However, the correlations between IR, metabolic syndrome (MS), and serum HCV RNA levels are still controversial. The aim of this study was to determine the relationships between IR, MS, and HCV RNA in patients with chronic genotype 1 or 2 HCV infection. METHODS One hundred and twenty subjects with chronic genotype 1 or 2 HCV infection with complete clinical data were prospectively enrolled. Baseline and laboratory data were collected and analyzed. IR was defined as a homeostatic model assessment- IR (HOMA-IR) score > 2.5. RESULTS Of the 120 patients, 47 (39.2%) had a HOMA-IR > 2.5, and 42 (35%) met the criteria for MS. IR was significantly associated with a high body mass index (p < 0.0001), high waist circumference (p < 0.0001) and high triglyceride level (p = 0.025). IR was an independent predictor of MS. However, in multivariate linear regression analysis, the serum HCV RNA level was not significantly different in chronic hepatitis C patients with or without IR (p = 0.761), and with or without MS (p = 0.292). CONCLUSIONS IR and MS are not uncommon in patients with chronic hepatitis C. The serum HCV RNA level is not associated with the presence of IR or MS in chronic hepatitis C patients with genotype 1 or 2 infection. The impact of hepatitis C virus on IR is not dose responsive.

Three new cembranoids crassocolides N-P (1-3), was isolated from the organic extract of a Formosan soft coral Sarcophyton crassocaule. These structures were elucidated on the basis of spectroscopic analyses and by comparison with those previously reported in literature. The cytotoxicity of these compounds toward various cancer cell lines has also been determined.

Epigenetic modifications like DNA methylation and histone acetylation play an important role in a wide range of brain disorders. Histone deacetylases (HDACs) regulate the homeostasis of histone acetylation. Histone deacetylase inhibitors, which initially were used as anticancer drugs, are recently suggested to act as neuroprotectors by enhancing synaptic plasticity and learning and memory in a wide range of neurodegenerative and psychiatric disorders, such as Alzheimer's disease (AD) and Parkinson's disease (PD). To reveal the physiological roles of HDACs may provide us with a new perspective to understand the mechanism of AD and to develop selective HDAC inhibitors. This paper focuses on the recent research progresses of HDAC proteins and their inhibitors on the roles of the treatment for AD.

SAR development of indole-based palm site inhibitors of HCV NS5B polymerase exemplified by initial indole lead 1 (NS5B IC(50)=0.9 μM, replicon EC(50)>100 μM) is described. Structure-based drug design led to the incorporation of novel heterocyclic moieties at the indole C3-position which formed a bidentate interaction with the protein backbone. SAR development resulted in leads 7q (NS5B IC(50)=0.032 μM, replicon EC(50)=1.4 μM) and 7r (NS5B IC(50)=0.017 μM, replicon EC(50)=0.3 μM) with improved enzyme and replicon activity.

Alzheimer's disease (AD) is one of the most common forms of neurodegenerative disease. Amyloid-β peptide (Aβ) is the most crucial molecule related to the pathological development of AD. Amyloid-β protein precursor (AβPP) is one of AβPP family members with conserved type I transmembrane. The genetic mutations of AβPP and the abnormity of its post-transcription and proteolytic processing contribute to the elevation of Aβ. The accumulation of Aβ in senile plaques is believed to be the most important event in AD pathology. Therefore, as a key upstream molecule of Aβ, AβPP is related to the AD pathology, but the biological function of AβPP is still not fully clear. AβPP-like proteins are widely expressed in multicellular eukaryotes. AβPP-like homologous genes and proteins are highly conserved in various organisms from invertebrates to mammals. AβPP-like genes undergo similarly pathways of transcription and post-transcription processing, and AβPP-like proteins is proteolyzed by the similar α-cleavage and the β-cleavage pathways. Based on the homology and the resemble domains, AβPP may play similar roles in organisms. In this article, we reviewed homology and structures of AβPP family members in organisms and further discussed potential biological function in normal and AD brains.